The Role of the Plasminogen Activation System in Cancer

Abstract

Hemostatic disorders are frequently observed in patients with malignancy with a significant proportion developing thrombotic and/or hemorrhagic complications including disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT), and thrombocytopenia. Together, these abnormalities are the second most common cause of mortality in cancer patients, which has led many investigators to try to unravel the pathogenesis of thromboembolic disease, in the eventuality that this will lead to novel therapeutic treatments. The plasminogen activation system is one pathway that has been consistently implicated in cancer. Its relevance to cancer extends from being responsible for many of the hemorrhagic episodes that occur in cancer patients to being fundamental to many, if not all of the molecular mechanisms that define tumor progression. Recent developments of clinical significance shall be reviewed with respect to the role of the plasminogen activation system in tumor growth and metastasis dissemination and in the thrombophilic state in the cancer patient.

Variations of components of the plasminogen activation system with the cell cycle in benign prostate tissue and prostate cancer

“…Furthermore, PAI-1 can also modulate integrin-dependent migration and u-PAR-dependent adhesion on vitronectin. These other nonproteolytic functions may be responsible for the observed effects of PAI-1 in metastasis dissemination (2,3). Clinically, PAI-1 has been reported as a potent predictor of metastases in lung and kidney cancer and as a predictor for poor response to tamoxifen therapy in recurrent breast cancer (31)(32)(33).…”

“…Therefore, a local feedback loop for the production of fibrinolytic components between tumor and stromal cells is likely to exist, leading to an altered expression of PAs and plasminogen inhibitors by the tumor. Because the activation of these proteases does not only directly induce pericellular proteolysis, an interaction with other proteins such as plasminogen, vitronectin, integrins, and ␣2-macroglobulin receptor are also involved in tumor propagation (2,37,38).…”

“…The role of u-PA in the development of tumor cell invasion and metastasis has been well established. However, t-PA has primarily a thrombolytic function and its role in tumor progression is still controversial (1,2). The activity of PAs, in turn, is regulated by binding to their receptors, most importantly the urokinase-type plasminogen activator receptor (u-PAR) and the plasminogen activator inhibitor type 1 (PAI-1).…”

“…Plasmin generation allows tumor and vascular cell invasion and angiogenesis as well as activation of latent growth factors, cytokines, and metalloproteases. Apart from mediating plasmin formation, components of the fibrinolytic system have other nonproteolytic functions that may also be important for tumor progression (2,3).…”

The overview of brinolysis system contemporary concepts and of its disorders diagnostic methods

“…Оральный прием транек-самовой кислоты нормализует состояние гемостаза у таких пациентов [62]. Повышенный уровень ПАИ-1 связывают с различимыми патологиями ССС [63], онкологией [64], ожирением, сахарным диабетом 2-го типа [65] и др.…”